Naturally occurring phosphonate

Few papers have appeared during the past year which have dealt with naturally occurring phosphonates. A diacylglyceryl ester of 2-aminoethylphosphonic acid (17)... 

Aminoethylphosphonate.—n.m.r. measurements indicate that 78% of the phosphorus present in a water-soluble glycoprotein from the sea anemone Metridium dianthus is in the phosphonate form and includes 2-aminoethyl-phosphonic acid (20). N.m.r. for the identification of naturally occurring phosphonates appears to be a technique superior to chromatography, which has been used hitherto. ... 

Most common naturally occurring phosphonate, found in a variety of organisms. 

The identification of a naturally occurring phosphonate was by Horiguchi and Kandatsu [134], who identified 2-aminoethylphosphonic acid in an amino acid extract from a hydrolysate of rumen protozoal lipid. Subsequently, it has been shown that phosphonates occur naturally in a variety of organisms. Consequently, there is a growing need to develop new and efficient synthetic methods for preparation of organophosphorus compounds bearing a P-C bond. 

Naturally occurring phosphonates were first discovered in 1959 when Horiguchi and Landatsu [10] isolated 2-aminoethylphosphonic acid (AEP) from the anemone (Chapter 6.5). Since that date other alkylphosphonic acids, a few phosphinates and some phosphonolipids and phosphonopeptides have been detected as minor components of various living species (11.135). Synthetic phosphonate DNA was reported in 1996 (Chapter 10.4) [11]. 

It is believed that 3-phosphonopyruvate may be the precursor of all naturally occurring phosphonates. It is obtained by the enzyme-catalysed reaction. 

The Role of Phosphonates in Living Systems, Hilderbrand, R.L., Ed., CRC Press, Boca Raton, FL, 1983 — Contributed chapters survey the role of naturally occurring organophosphorus compounds (containing a C-P bond) in biological systems and the use of a wide variety of organophosphorus compounds for the regulation of metabolism and the treatment of disease. 

Fig. 4 Lerner s group used phosphonate [3] as the hapten to raise an antibody which was capable of hydrolysing the ester [5] shown alongside it. Schultz found that naturally occurring antibodies using phosphate [4] as their antigen could hydrolyse the corresponding p-nitrophenyl choline carbonate [6]. (Those parts of haptens [3] and [4] required for antibody recognition have been emphasized with bold bonds.)...

The lipids of some organisms, such as Tetrahymena, contain aminoethylphosphonate, a compound with a C-P bond (Chapter 8). There are also many other naturally occurring phosphono compounds and huge quantities of synthetic phosphonates, present in detergents, herbicides, and insecticides, are metabolized by bacteria 297 Here we will consider only one step in the biosynthesis of phosphonates, the conversion of PEP into phosphonopyruvate (Eq. 13-54), a reaction catalyzed by PEP mutase. The phospho group is moved... 

A few other biologically interesting and naturally occurring peptides and amino acids of rather simple structure were synthesized using the Ugi four-component reaction (Figure 12.5) the phosphonic acid antibiotics plumbemycin A 249 and B 250 [126], both epimers of the polychlorinated antihypertensive peptide (+)-demethyldysidenin 251 [127], and the nucleoside antibiotic nikkomycin 252 [128]. 

Olefination of aldehydes with a-silyl- and a-stannyl-stabilized phosphonate carbanions derived from cyclo-[L-AP4-D-Val] allow a (Z)-selective access to a,p-substituted vinyl phosphonates (343) that have been transformed into enantiomerically pure 4-alkylidene 4PA derivatives (344) (Figure 54). " Electrophilic fluorination of lithiated bis-lactim ethers derived from cyclo-[L-AP4-D Val] (345) with commercial NFSi allow direct access to a-monofluor-inated phosphonate mimetics of naturally occurring phosphoserine (346) and phosphothreonine (347), in enantiomerically pure form and suitably protected for solid-phase peptide synthesis (Figure 55). ... 

Hildebrand, R.L., The Role of Phosphonates in Living Systems, CRC Press, Boca Raton, 1983. Hildebrand, R.L., Curley-Joseph, J, Lubansky, H.J., and Henderson, T.O., Biology of alkylphosphonic acids. A review of the distribution, metabolism, and structure of naturally occurring alkylphosphonic acids, in Topics in Phosphorus Chemistry, Vol. 11, John Wiley Sons, New York, 1983, pp. 297-338. Hudson, H.R., Quasi-phosphonium intermediates and compounds, in Topics in Phosphorus Chemistry, Vol. 11, John Wiley Sons, New York, 1983, pp. 339-436. 

Considerable interest has been directed to the biodegradation of phosphonates which contain the rather unusual C-P bond since a number of them are naturally occurring compounds, and one of them—glyphosate—has been extensively used as a herbicide. 

Syntheses of a variety of naturally occurring polyene and polyenyne amides have been reported. Pepper alkaloids have been obtained using the Wittig reaction and phosphonate, e.g., (167), - routes. 

The scarcity of unnatural D-amino acids makes these compounds attractive synthetic targets, especially when one considers the disparity of price relative to their naturally occurring partners. If the hydroxyl group of an L-lactate could be displaced by a nitrogen nucleophile with inversion of configuration, this would allow easy access to D-alanine derivatives. Such a transformation can be realized by the reaction of 2 with diphenyl phosphorylazide and DBU to produce the (R)-azidoester 96 (98% ee) [33]. The initial step of the reaction is the formation of phosphonate 95. The resulting liberated azide then completely displaces the phosphonate group, with nearly total inversion of the stereo center. 

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